DESCRIPTION: This project is focused upon determining the molecular genetic basis for alterations in transport that render cells resistant to antifolates by preventing drug accumulation. A full length cDNA will be cloned by preparing an expression library from the Chinese hamster lung cell line DC- 3F/FA3 that appears to overexpress a gene for a 43.2 kd glycoprotein associated with enhanced folate uptake. Functional interactions of this and the hp58 gene product will be studied and used to isolate putative mutant transporters from existing cell lines.